BACKGROUND:The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE:The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS:The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS:The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 μg mL-1. CONCLUSION:This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Conventional hydrogels exhibit good performance in various biomedical applications. They consist of a three-dimensional network with porous structures that are constructed from synthetic or natural polymers through physical or chemical cross-linking. However, a critical challenge lies in their vulnerability to mechanical damage, as conventional hydrogels often fail to maintain structural integrity under minor trauma. In response to this issue, self-healing hydrogels can autonomously repair themselves after damage, restoring their original functionality without needing external intervention. This remarkable capability significantly extends the lifespan of critical products, including wound dressings, biosensors, drug delivery and tissue engineering scaffolds. This review summarizes the synthesis mechanisms while emphasizing the latest application research advancements. By highlighting the distinct benefits of self-healing hydrogels, we systematically review recent progress in synthesis methods. Our goal is to provide valuable insights that will help researchers in designing and developing more efficient self-healing hydrogels, paving the way for enhanced biomedical solutions.

Mesoporous organosilica nanoparticles (MONs) are promising drug carriers with excellent biocompatibility and biodegradability. In the context of the bacterial infection microenvironment, a hyaluronidase (HAase)/glutathione (GSH) dual-responsive degradable nanoplatform based on MON (ICG/CIP@MON@PEI-HA) has been developed for the multimodal treatment of bacterial infection. In this work, ciprofloxacin (CIP) and indocyanine green (ICG) are physically adsorbed into the MON, polyethyleneimine (PEI) is electrostatically adsorbed onto the MON surface, and hyaluronic acid (HA) is grafted onto the amino groups of PEI via the amide bonds. The overexpression of HAase at bacterial infection sites enables HA shell degradation, and positively charged PEI is exposed, which facilitates nanoparticle binding to negatively charged bacteria. Also, owing to the protonation of amine groups, PEI is swelled in the acidic environment of bacterial infection, which favours drug release. Subsequently, overexpressed GSH breaks the disulfide bonds in the MON, triggering structural degradation that inhibits carrier accumulation and accelerates drug release even further. According to in vitro antibacterial evaluations, the antibacterial effect can be enhanced to 100% when phototherapy and pharmaceutical therapy are combined. In vitro cytotoxicity assays have demonstrated that ICG/CIP@MON@PEI-HA possesses excellent biocompatibility. Therefore, this study offers a potential approach for developing biodegradable nanoplatforms for the combined treatment of bacterial infection.

Bovine serum albumin, based on its low toxicity and excellent biocompatibility, has great potential as a carrier for drug delivery systems. In this context, a pH/GSH dual-responsive drug delivery system (ICG/DOX@Fe-BSA-FA nanoparticles) based on Bovine serum albumin (BSA) is constructed for tumor-targeted multimodal therapy. In this study, doxorubicin (DOX) and indocyanine green (ICG) are co-loaded after Fe3+ is coordinated with BSA, and the system is finally grafted with the targeted molecule Folic acid. DOX is used in chemotherapy, ICG is used in photodynamic therapy (PDT) and photothermal therapy (PTT), and Fe3+ mainly provided sufficient raw material for the Fenton-like reaction. The ability of ICG/DOX@Fe-BSA-FA (ID@FBF) nanoparticles to combine chemotherapy with CDT/PDT/PTT is demonstrated by several physical characterization. In vitro cell uptake assay and in vitro cytotoxicity assay demonstrated the excellent ability of ID@FBF to target 4T1 cells and kill tumor cells with the IC50 value of 0.75 mu g mL-1. Therefore, chemotherapy combined with CDT/PDT/PTT therapy may result in satisfactory efficacy via ID@FBF, a potentially powerful and highly effective nanosystem. In this context, a pH/GSH dual-responsive drug delivery system (ICG/DOX@Fe-BSA-FA nanoparticles) based on Bovine serum albumin (BSA) is constructed for tumor-targeted multimodal therapy. In this study, doxorubicin (DOX) and indocyanine green (ICG) are co-loaded after Fe3+ is coordinated with BSA, and the system is finally grafted with the targeted molecule Folic acid. image

Abstract In this study, N-doped TiO2-Fe2O3/C nanostructure is prepared by mixing of the precursors of both metals (Ti and Fe) with the N doped ligand precursor in the same process and further being calcined at 500oC directly in air atmosphere. Herein, other three different Ti-MOFs precursors and its derivatives were also obtained in the same way for comparison of structure and performance. Interestingly, the obtained products derived from N doped bimetallic Ti-Fe MOFs display a particularly dendritic structure with large surface area and well mesoporous structures. Meanwhile, it was further confirmed from FTIR and XPS results that the derivatives were still retain N and C components after calcination in air condition which is beneficial to improve the photocatalytic activity. Finally, the prepared N doped dendritic bimetallic structure as a photocatalyst to decompose methylene blue (MB) dye. It was showed that N-doped TiO2-Fe2O3/C demonstrates better photocatalytic performance than that of N-doped TiO2/C and non-N-doped TiO2/C and the MB degradation efficiency of N-doped TiO2-Fe2O3/C reaches 81%.

In the context of the tumor microenvironment, the design of a high concentration glutathione (GSH) driven degradation drug delivery system (ID@MON-HA) is according to a different quantity of GSH to normal tissues. This system involves loading doxorubicin (DOX) and new indocyanine green (IR820) onto mesoporous organosilica nanoparticles (MON). The disulfide linkages in MON are broken in response to high amounts of GSH in tumor cells, resulting in the degradation of the overall structure and preventing carrier accumulation. To connect the hyaluronic acid (HA) and the carrier with encapsulated drugs, a pH-sensitive Schiff based bond is utilized. Furthermore, MON specifically target to tumor sites due to the selective binding of HA to tumor cells that overexpress the CD44 receptor. Experiments have shown that increased GSH concentrations and pH levels below physiological can accelerate drug release. Additionally, in vitro cellular experiments have demonstrated that combining chemotherapy and phototherapy enhances the suppression of tumor cells (median inhibition concentration IC50 = 1.53 mu g mL_1). These findings indicate that the study offers an acceptable approach for developing degradable nanoplatforms for tumor combination therapy.

It is crucial to precisely strike the bacterially infected area and avoid damaging healthy tissue in bacterial infection treatment. Herein, we report an acidity-triggered aggregation antibacterial nanoplatform based on biodegradable mesoporous organic silica nanoparticles (MON NPs). The surface of MON NPs modified with polydopamine (PDA) encapsulated ciprofloxacin (CIP) and methylene blue (MB) and was then further grafted with glycol chitosan to obtain MB/CIP@MON-PDA-GCS NPs (MCMPG NPs). In the bacterial infection environment with acidic characteristics, glycol chitosan (GCS) becomes positively charged. Consequently, the positively charged acidity-triggered GCS enables MCMPG NPs to accumulate on the negatively charged bacterial surfaces in the infected area and not in healthy tissue. The targeted method allows for the precise release of CIP and MB, ensuring the spatial accuracy of photodynamic therapy (PDT) and photothermal therapy (PTT) for effective bacteria-specific treatment. An acidity-triggered aggregation antibacterial nanoplatform based on biodegradable mesoporous organic silica nanoparticles, is reported. It enables precise drug release and spatial accuracy for photodynamic therapy and photothermal therapy.

Due to its low adverse effects, minimal invasiveness, and outstanding patient compliance, photodynamic therapy (PDT) has drawn a great deal of interest, which is achieved through incomplete reduction of O-2 by a photo-sensitizer under light illumination that produces amounts of reactive oxygen species (ROS). However, tumor hypoxia significantly hinders the therapeutic effect of PDT so that tumor cells cannot be eliminated, which results in tumor cells proliferating, invading, and metastasizing. Additionally, O-2 consumption during PDT exacerbates hypoxia in tumors, leading to several adverse events after PDT treatment. In recent years, various investigations have focused on conquering or using tumor hypoxia by nanomaterials to amplify PDT efficacy, which is summarized in this review. This comprehensive review's objective is to present novel viewpoints on the advancement of oxygenation nanomaterials in this promising field, which is motivated by hypoxia-associated anti-tumor therapy.

Surface modification of hollow mesoporous silica nanoparticles (HMSNs) with unique advantages are highly promising for drug delivery and have emerged for effective cancer treatment. In this study, functionalized nanoparticles for targeting and dual-responsive release of loaded doxorubicin hydrochloride (DOX center dot HCL) and indocyanine green (ICG) (labeled as ID@HCH). In addition, chitosan (CS) was conjugated onto the HMSNs as capping agents and then dialdehyde hyaluronic acid (HDA) was modified to endow the ability to target the CD44 receptor. The characterizations demonstrated that nanocarriers have been successfully constructed with excellent drug loading capacity (DL) and drug entrapment efficiency (EE). The in vitro DOX control release displayed pH/enzyme-response properties owing to the pH-dependent swelling effect of chitosan and the HDA degraded by hyaluronidases (HAase). Moreover, the results of in vitro cell experiments proved that the ID@HCH could inhibit the cancer cells viability via accurately targeting HepG2 cells and chemotherapy combined with photodynamic therapy. This study demonstrated that ID@HCH is a new promising dual-responsive drug delivery system for chemotherapy and photodynamic therapy.

Nanomaterial-based cancer therapy faces significant limitations due to the complex nature of the tumor microenvironment (TME). Starvation therapy is an emerging therapeutic approach that targets tumor cell metabolism using glucose oxidase (GOx). Importantly, it can provide a material or environmental foundation for other diverse therapeutic methods by manipulating the properties of the TME, such as acidity, hydrogen peroxide (H2O2) levels, and hypoxia degree. In recent years, this cascade strategy has been extensively applied in nanoplatforms for ongoing synergetic therapy and still holds undeniable potential. However, only a few review articles comprehensively elucidate the rational designs of nanoplatforms for synergetic therapeutic regimens revolving around the conception of the cascade strategy. Therefore, this review focuses on innovative cascade strategies for GOx-based synergetic therapy from representative paradigms to state-of-the-art reports to provide an instructive, comprehensive, and insightful reference for readers. Thereafter, we discuss the remaining challenges and offer a critical perspective on the further advancement of GOx-facilitated cancer treatment toward clinical translation. Nanomaterial-based cancer therapy faces significant limitations due to the complex nature of the tumor microenvironment (TME).

Combination therapy is an effective way to alleviate the shortcoming of monotherapy and enhances therapeutic efficacy. Herein, a distinctive hollow mesoporous silica nanoparticle (HMSNs) encapsulated with folic acid-modified bovine serum albumin (BSA-FA), denoted as HBF, was engineered for tumor targeting and dual-responsive release of loaded-therapeutic agents MD (methylene blue (MB) and doxorubicin (DOX)). The BSA molecule as a ''gatekeeper'' prevents premature drug leakage and actively unloads the cargos through BSA detachment in response to intracellular glutathione (GSH). Folic acid (FA) promotes the specific intracellular delivery of the drug to folate receptor (FR)-expressing cancer cells to improve the efficacy of chemo-photodynamic therapy (PDT). In vitro drug release profiles showed that the drug carrier could achieve pH/redox-responsive drug release from MD@HBF owing to the cleavage of the imine bonds between HMSNs-CHO and BSA-FA and BSA intramolecular disulfide bond. Additionally, a series of biological evaluations, such as cell uptake experiments, toxicity experiments, and in vivo therapeutic assays indicated that MD@HBF possesses the features of accurately targeting FR-expressing 4T1 cells to induce cells apoptosis in vitro, exhibits outstanding tumor cell synergistic killing efficiency of chemo-photodynamic therapy (combination index CI = 0.325), and inhibits tumors growth. These results demonstrated that the strategy of combining HMSNs with stimuli-responsive biodegradable protein molecules could provide a new potential direction toward the ''on-demand'' drug release for precision chemo-photodynamic therapy in cancer treatment.

HMSNs are coated with oxidized hyaluronic acid (OHA) by a pH-sensitive Schiff base bond and a redox-sensitive disulfide bond.

The combination of chemotherapy and phototherapy has become a promising cancer treatment strategy. In this study, a pH/NIR dual-responsive hollow mesoporous silica nanoparticles (HMSNs) based nanocarrier for co -delivering doxorubicin hydrochloride (DOX) and indocyanine green (ICG) was developed. DOX was loaded for chemotherapy and ICG for photothermal therapy (PTT) and photodynamic therapy (PDT). This system targets the asialoglycoprotein receptor (ASGPR) in over-expressing human hepatocellular liver carcinoma cells (HepG2) by linking HMSNs and lactobionic acid (LA)-modified dialdehyde chitosan (DACS) via Schiff base bonds. It is demonstrated that HMSNs-DACS-LA have been successfully prepared through various physical characterizations. Drug release tests revealed that it had the characteristics of properties of pH/NIR dual-responsive. In vitro cellular uptake and cytotoxicity assay showed that ID@HMSNs-DACS-LA could target HepG2 cells and reduced the ac-tivity of tumor cells. Therefore, co-delivery of ICG and DOX via HMSNs-DACS-LA nanocarriers may provide a feasible strategy for tumor-targeted combined chemotherapy and phototherapy.

Chemotherapy combined with photothermal therapy, a promising strategy for cancer treatment, has a high potential to control drug release and improve therapeutic efficacy. Inspired by this, a pH/NIR dual-responsive drug delivery system (DOX/HMSN@PDA-HA nanoparticles, simplified as DHPH NPs) based on hollow mesoporous silica nanoparticles (HMSNs) was designed for targeted therapy of tumor, by self-coating polydopamine-modified hyaluronic acid (HA-PDA) layer. Doxorubicin (DOX) was loaded into HMSNs for chemotherapy, while HA-PDA coating acted as photothermal therapy agent with tumor-targeted capability. Characterizations suggest that DHPH nanoparticles have been successfully constructed with excellent drug loading capacity (36.91%) and satisfactory photothermal conversion efficiency (25.74%). Furthermore, in vitro results indicate that DHPH nanoparticles could precisely target human hepatocellular liver carcinoma cells and effectively suppress the tumor cells growth under 808 nm laser irradiation (2 W cm−2). Therefore, this study presents a feasible strategy for developing efficient platform for tumor-targeted chemo-photothermal therapy.

The design and development of multifunctional nano-drug delivery systems (NDDSs) is a solution that is expected to solve some intractable problems in traditional cancer treatment. In particular, metal-organic frameworks (MOFs) are novel hybrid porous nanomaterials which are constructed by the coordination of metal cations or clusters and organic bridging ligands. Benefiting from their intrinsic superior properties, MOFs have captivated intensive attentions in drug release and cancer theranostic. Based on what has been achieved about MOF-based DDSs in recent years, this review introduces different stimuli-responsive mechanisms of them and their applications in cancer diagnosis and treatment systematically. Moreover, the existing challenges and future opportunities in this field are summarized. By realizing industrial production and paying attention to biosafety, their clinical applications will be enriched.

A novel nanodrug delivery system (NDDS) based on block copolymers of Poly(DEA)-block-Poly(PgMA) (PDPP) was developed to enhance in vitro cellular uptake and anticancer efficacy. pH-responsive doxorubicin (DOX) based small molecule prodrug (DOX-hyd-N3) and mPEG-N3 were co-conjugated onto PDPP via copper-catalyzed "Click chemistry" to give a dual pH-responsive polymeric prodrug (mPEG-g-PDPP-g-hyd-DOX), which could be self-assembled into core-shell polymeric micelles (M(DOX)) with particles size of 81 +/- 1 nm in aqueous phase. Additionally, the pH-responsive charge-reversal, stability and drug release behaviour at different pHs were then evaluated. Moreover, the surface charge of M(DOX) could quickly convert from negative (-6.64 +/- 3.37 mV) to positive (5.35 +/- 1.33 mV) thanks to the protonation of Poly(DEA) moieties as the pH value decreased from 7.4 during blood circulation to 6.5 in extracellular of tumour tissues. Meanwhile, according to the cytotoxicity determined by CCK-8 assay, cellular uptake, flow-cytometric and apoptosis profiles of two human cancer cell lines (HeLa and SW480), we could draw the conclusion that the cellular uptake and anticancer efficacy were significantly enhanced when cells were incubated with micelles at pH 6.5 due to the charge-reversal of micelles from negative to positive. With the protonation of Poly(DEA) moieties in acidic extracellular microenvironment and the pH-responsive DOX release with hydrazone linkage in endo/lysosome pH, this dual pH-responsive charge-reversal micelle platform might become an encouraging strategy for more effective cancer treatment.

Hollow mesoporous silica nanoparticles (HMSNs) served as nanocarriers for transporting doxorubicin hydrochloride (DOX) and indocyanine green (ICG) and were incorporated into a pH-sensitive targeted drug delivery system (DDS). Boronate ester bonds were employed to link HMSNs and dopamine-modified hyaluronic acid (DA-HA), which acted as both the "gatekeeper" and targeting agents (HMSNs-B-HA). Well-dispersed HMSNs-B-HA with a diameter of about 170 nm was successfully constructed. The conclusion was drawn from the in vitro drug release experiment that ICG and DOX (ID) co-loaded nanoparticles (ID@HMSNs-B-HA) with high drug loading efficiency could sustain drug release under acidic conditions. More importantly, in vitro cell experiments perfectly showed that ID@HMSNs-B-HA could well inhibit murine mammary carcinoma (4T1) cells via chemotherapy combined with photodynamic therapy and accurately target 4 T1 cells. In summary, all test results sufficiently demonstrated that the prepared ID@HMSNs-B-HA was a promising nano-DDS for cancer photodynamic combined with chemotherapy.

Hollow mesoporous silica nanoparticles (HMSNs) have become an attractive drug carrier because of their unique characteristics including stable physicochemical properties, large specific surface area and facile functionalization, especially made into intelligent drug delivery systems (DDSs) for cancer therapy. HMSNs are employed to transport traditional anti-tumor drugs, which can solve the problems of drugs with instability, poor solubility and lack of recognition, etc., while significantly improving the anti-tumor effect. And an unexpected good result will be obtained by combining functional molecules and metal species with HMSNs for cancer diagnosis and treatment. Actually, HMSNs-based DDSs have developed relatively mature in recent years. This review briefly describes how to successfully prepare an ordinary HMSNs-based DDS, as well as its degradation, different stimuli-responses, targets and combination therapy. These versatile intelligent nanoparticles show great potential in clinical aspects.

In this work, a pH-responsive and tumor targeted multifunctional drug delivery system (RB-DOX@HMSNs-N = C-HA) was designed to realize chemo-photodynamic combination therapy. Hollow mesoporous silica nanoparticles (HMSNs) was served as the host material to encapsulate doxorubicin (DOX) and photosensitizer rose bengal (RB). Hyaluronic acid (HA) was modified on the surface of HMSNs via pH-sensitive Schiff base bonds as gatekeeper as well as targeted agent. Characterization results indicated the successful preparation of HMSNs-N = C-HA with appropriate diameter of 170 nm around and the nanocarriers displayed superior drug loading capacity (15.30 % for DOX and 12.78 % for RB). Notably, the results of in vitro drug release experiments confirmed that the system possessed good pH-sensitivity, which made it possible to release cargoes in slight acid tumor micro-environments. Significantly, the in vitro cell uptake and cytotoxicity assay results fully proved that RB-DOX@HMSNs-N = C-HA could precisely target murine mammary carcinoma (4T1) cells and effectively inhibit tumor cells viability with chemo-photodynamic synergistic therapy. Overall, our work (RB-DOX@HMSNs-N = C-HA) provides an efficient approach for the development of chemo-photodynamic combination therapy.

Although electrospinning of nanofibrous scaffolds benefit to wound healing have been developed at a fast pace, achieving nanofibrous scaffolds with high absorptivity by green electrospinning and crosslinking techniques is still a great challenge. Here, we developed a maleilated hyaluronate/methacrylated poly (vinyl alcohol) (MHA) (MaPVA) composite nanofibers by electrospinning from pure water solvent and followed by photopolymerization to form crosslinking nanofibers network. Electrospinnability of MHA/MaPVA blend systems were investigated and the results shows that the morphology and diameter of the nanofibers were mainly affected by MHA/MaPVA weight ratios by changing viscosity and conductivity of the blend solutions. The crystalline microstructure of the electrospun fibers was not well developed due to intermolecular hydrogen bonding interaction between the molecules of MHA and MaPVA. The photocrosslinking MHA/MaPVA nanofibrous mats can swell to form fibrous hydrogels with high water absorption, meanwhile it is cytocompatible and capable of promoting the cell attachment, which render it great potential for wound dressings.